"The U.S. Food and Drug Administration today approved Opsumit (macitentan), a new drug to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive and debilitating disease that can lead to death or the need for lung transpla"...
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Clinical Trials Experience
Studies in Premature Infants at Risk for Respiratory Distress Syndrome
The safety data described below reflect exposure to SURFAXIN at a dose of 5.8 mL per kg (up to 4 doses) administered in either 4 aliquots (Study 1) or 2 aliquots (Study 2) in 643 infants 32 weeks gestational age or less in 2 randomized double-blind, active-controlled clinical studies in which infants could receive up to 4 doses of surfactant intratracheally [see Clinical Studies]. Study 1 was conducted in 1294 premature infants who weighed between 600 g and 1250 g at birth and were 32 weeks or less in gestational age. Infants received 1 of 3 surfactants, SURFAXIN (N = 524), colfosceril palmitate (N = 506), or beractant (N = 258). Study 2 was conducted in 252 premature infants who weighed between 600 g and 1250 g and were less than 29 weeks in gestational age. Infants received SURFAXIN (N = 119) or poractant alfa (N = 124).
Comparator surfactants colfosceril palmitate and beractant were administered at the recommended doses (5.0 and 4.0 mL per kg, respectively) while the first dose of poractant alfa administered (2.2 mL per kg) was less than the recommended dose of 2.5 mL per kg. Any subsequent doses of poractant alfa were at the recommended 1.25 mL per kg dose.
Administration-related adverse reactions (endotracheal tube reflux, pallor, endotracheal tube obstruction, and need for dose interruption) were assessed in both SURFAXIN controlled clinical studies. Overall, the incidence of administration-related adverse reactions was higher in infants who received SURFAXIN compared to other surfactants (Table 2) and resulted in a greater proportion of infants treated with SURFAXIN who experienced administration-related oxygen desaturation and bradycardia. For Study 1, oxygen desaturation was reported in 17%, 9%, and 13% and bradycardia for 5%, 2%, and 3% of infants treated with SURFAXIN, colfosceril palmitate, and beractant, respectively. For Study 2, oxygen desaturation was reported in 8% and 2% and bradycardia in 3% and 2% of infants treated with SURFAXIN and poractant alfa, respectively. These adverse reactions did not appear to be associated with an increased incidence of serious complications or mortality relative to the comparator surfactants (Table 3).
Table 2: Administration-Related Adverse Reactions in
SURFAXIN Controlled Clinical Studiesa
|Study 1b||Study 2c|
(N = 524)
(N = 506)
(N = 258)
(N = 119)
(N = 124)
|Total Doses Administered||994||1038||444||174||160|
|Total Number of Events (Events per 100 Doses)|
|ETT Reflux||183 (18)||161 (16)||67 (15)||47 (27)||31 (19)|
|Pallor||88 (9)||46 (4)||38 (9)||18 (10)||7 (4)|
|Dose Interruption||87 (9)||46 (4)||30 (7)||7 (4)||2 (1)|
|ETT Obstruction||55 (6)||21 (2)||19 (4)||27 (16)||1 (1)|
|aTable includes only infants who received study treatment.
b In Study 1 doses were administered in 4 aliquots.
c In Study 2 doses were administered in 2 aliquots.
Table 3: Common Serious Complications
Associated with Prematurity and RDS in SURFAXIN Controlled Clinical Studies
Through 36-Weeks Post-Conceptual Age (PCA)
|Study 1||Study 2|
(N = 527)
(N = 509)
(N = 258)
(N = 119)
(N = 124)
|Intraventricular hemorrhage, all grades||52||57||54||39||38|
|- Grade 3/4||19||18||21||13||8|
|Patent ductus arteriosus||37||35||37||43||44|
|Retinopathy of prematurity, all grades||27||26||25||32||31|
|Necrotizing enterocolitis, all grades||17||17||19||13||15|
|Pulmonary air leak through Day 7, all types||15||17||14||9||7|
|-Pulmonary interstitial emphysema||9||10||10||3||5|
Adverse reactions reported in the controlled clinical studies through 36-weeks PCA occurring in at least 10% of infants were anemia, jaundice, metabolic acidosis, oxygen desaturation, hyperglycemia, pneumonia, hyponatremia, hypotension, respiratory acidosis, and bradycardia. These reactions occurred at rates similar to the comparator surfactants.
No assessments for immunogenicity to SURFAXIN were performed in these clinical studies.
Twelve-month corrected-age follow-up of 1546 infants enrolled in the 2 controlled clinical studies demonstrated no significant differences in mortality or gross neurologic findings between infants treated with SURFAXIN and those treated with the comparator surfactants (colfosceril palmitate, beractant, or poractant alfa).
Clinical Study in Adults with ARDS
The safety and efficacy of lucinactant administered in 2 doses separated by 48 hours via segmental bronchoscopic lavage in adults with ARDS was evaluated in a two-part clinical trial in 124 adult patients. Twenty-two patients were studied in the initial open-label portion of the trial (Part A) and 102 patients participated in a subsequent randomized controlled portion (Part B). Compared to standard of care, patients who received treatment with lucinactant via segmental bronchoscopic lavage at doses up to 50 mL per lung segment had an increased incidence of death, multi-organ failure, sepsis, anoxic encephalopathy, renal failure, hypoxia/decreased oxygen saturation, pneumothorax, hypotension, and pulmonary embolism compared to those patients receiving standard of care. SURFAXIN is not indicated for use in the treatment of ARDS.
Read the Surfaxin (lucinactant) Side Effects Center for a complete guide to possible side effects
No information provided.
Last reviewed on RxList: 3/16/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Surfaxin Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.